a phase i safety and immunogenicity trial of hiv-1 gp120 c4-v3 hybrid polyvalent peptide immunogen mixed in mineral oil containing mannose mono-oleate (ifa)

Conditions: HIV Infections

Summary: to evaluate the safety of hiv-1 gp120 c4-v3 hybrid polyvalent peptide immunogen (c4-v3 peptides) formulated in mineral oil containing mannose mono-oleate (ifa) in hiv-1 uninfected volunteers. to evaluate the humoral and cellular immune responses to the c4-v3 peptides as measured by the induction of 1 or more of the following: neutralizing antibodies to hiv-1 mn and rf, cross-neutralizing antibodies to primary isolates of hiv-1, hiv-1 antigen-specific lymphoproliferation, cd8+ and cd4+ cytotoxic t lymphocyte (ctl) activity specific for hiv-1 gp120 or v3 peptides corresponding to the vaccine strains of hiv-1, induction of hla-b7 and hla-a2 restricted cd8+ctls, and induction of hiv-specific dth responses. the test immunogen (c4-v3 peptides) is constructed from 4 sequences of the hiv-1 v3 gp120 loop shared by approximately 80% of north american hiv-1 strains. because of the critical role that this region plays in generating anti-hiv sequences, it is hypothesized that the test immunogen (c4-v3 peptides) will be capable of inducing a broad range of cross-reactive neutralizing antibodies in the majority of recipients.

the test immunogen (c4-v3 peptides) is constructed from 4 sequences of the hiv-1 v3 gp120 loop shared by approximately 80% of north american hiv-1 strains. because of the critical role that this region plays in generating anti-hiv sequences, it is hypothesized that the test immunogen (c4-v3 peptides) will be capable of inducing a broad range of cross-reactive neutralizing antibodies in the majority of recipients. twenty-eight volunteers are randomized to receive two 0.5 ml injections of c4-43 peptides in ifa or placebo (ifa alone) administered intramuscularly at 0, 1, 6, and 12 months. at least 50% of all volunteers (6 per groups i and ii; 2, group iii) must be hla-b7 phenotype.

Eligibility criteria:
inclusion criteria volunteers must have: * negative elisa for hiv within 8 weeks of immunization. * normal history and physical examination. * normal chest x-ray within 4 weeks prior to initial immunization. * low-risk sexual behavior as defined by aveg. exclusion criteria co-existing condition: volunteers with the following conditions are excluded: * medical or psychiatric condition that precludes compliance with the protocol, including recent suicidal ideation or present psychosis. * occupational responsibilities which preclude compliance with the protocol. * active syphilis (if the serology is documented to be a false positive or due to a remote \[more than 6 months\] treated infection, the volunteer is eligible). * active tuberculosis (volunteers with a positive purified protein derivative and a normal chest x-ray showing no evidence of tb and not requiring isoniazid therapy are eligible). * positivity for hepatitis b surface antigen. volunteers with the following prior conditions are excluded: * history of immunodeficiency, chronic illness, malignancy, or autoimmune disease. note: individuals with a history of cancer are excluded unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure. * history of suicide attempts or past psychosis. * history of anaphylaxis or other serious adverse reactions to vaccines. * history of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., stevens-johnson syndrome, bronchospasm, or hypotension). * history of lung disease. prior medication: excluded: * live attenuated vaccines within 60 days of study. note: medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) are not exclusionary, but should be given at least 2 weeks away from hiv immunizations. * experimental agents within 30 days prior to study. * hiv-1 vaccines or placebo, received in a previous hiv vaccine trial. * immunosuppressive medications. prior treatment: excluded: * receipt of blood products or immunoglobulin in the past 6 months. risk behavior: excluded: * alcohol intake greater than or equal to the equivalent of 1 oz of 100 proof per day (4 oz. glass of wine or 12 oz. of beer per day). * identifiable higher-risk behavior for hiv infection as determined by screening questions designed to identify risk factors for hiv infection; specific exclusions include a history of injection drug use within the last 12 months prior to enrollment and higher- or immediate-risk sexual behavior as defined by the aveg (i.e., meeting the criteria for aveg risk groups c and d).

Keywords: hiv antibodies hiv envelope protein gp120 drug carriers hypersensitivity, delayed aids vaccines cd4-positive t-lymphocytes cd8-positive t-lymphocytes hiv seronegativity neutralization tests mineral oil oleic acids mannose hla-b7 antigen hla-a2 antigen hiv preventive vaccine